Pyridineamine compounds useful as Pim kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9540347-B2
Application number	US-201615166380-A
Country	US
Kind code	B2
Filing date	May 27, 2016
Priority date	May 29, 2015
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

The present disclosure describes pyridineamine compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.

First claim

What is claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
X is N or CH;
ring A is C 6-10 aryl or 5-10 membered heteroaryl, said heteroaryl group consisting of one or more carbon atoms and 1, 2, or 3 heteroatoms selected from N, O and S, wherein the C 6-10 aryl or 5-10 membered heteroaryl is optionally substituted with 1 or 2 substituents independently selected from R A ;
R A is halogen, cyano, amino, or C 1-3 alkyl;
n is 0 or 1;
Cy A , when present, is selected from C 6-10 aryl, 5-10 membered heteroaryl, C 3-7 cycloalkyl, and 4-10 membered heterocycloalkyl, wherein the ring atoms of the 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl forming Cy A consist of one or more carbon atoms and 1, 2, or 3 heteroatoms selected from N, O and S, and wherein the C 6-10 aryl, 5-10 membered heteroaryl, C 3-7 cycloalkyl, and 4-10 membered heterocycloalkyl forming Cy A are each optionally substituted by 1, 2 or 3 substituents independently selected from R CyA ;
R CyA is halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, Cy B , -L-Cy B , ═O, CN, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 or S(O) 2 NR c1 R d1 ; wherein the C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl forming R CyA are each optionally substituted with 1, 2 or 3 substituents independently selected from halogen, C 1-3 haloalkyl, CN, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 and S(O) 2 NR c1 R d1 ;
Cy B is selected from C 6-10 aryl, 5-10 membered heteroaryl, C 3-7 cycloalkyl, and 4-10 membered heterocycloalkyl, wherein the ring atoms of the 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl forming Cy A consist of one or more carbon atoms and 1, 2, or 3 heteroatoms selected from N, O and S, and wherein the C 6-10 aryl, 5-10 membered heteroaryl, C 3-7 cycloalkyl, and 4-10 membered heterocycloalkyl forming Cy B are each optionally substituted with 1, 2, or 3 substituents independently selected from R CyB ;
R CyB is halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, CN, OH, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 NR c2 C(O)OR a2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 or S(O) 2 NR c2 R d2 , wherein the C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl forming R CyB are each optionally substituted with 1, 2 or 3 substituents independently selected from halogen, C 1-3 haloalkyl, CN, OH, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 NR c2 C(O)R b2 NR c2 C(O)NR c2 R d2 NR c2 C(O)OR a2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 and S(O) 2 NR c2 R d2 ;
L is C 1-4 alkylene, L 1 -O-L 1 , L 1 -C(═O)-L 1 , L 1 -OC(═O)-L 1 , L 1 -C(═O)O-L 1 , L 1 -NHC(═O)— L, L 1 -C(═O)NH-L, L 1 -NH-L 1 , L 1 -N(CH 3 )-L 1 , L 1 -NHC(═O)NH-L, L 1 -NHC(═O)O-L 1 , L 1 -S-L 1 , L 1 -S(═O)-L 1 , L 1 -S(═O) 2 -L 1 , L 1 -NHS(═O) 2 -L 1 , L 1 -S(═O) 2 NH-L 1 , L 1 -NHS(═O) 2 NH-L 1 , wherein L 1 , at each occurrence, is independently selected from a bond and C 1-2 alkylene; and wherein the C 1-2 alkylene forming L 1 is optionally substituted with 1 or 2 substituents independently selected from F, Cl, CN, OH, O(C 1-3 alkyl), NH 2 , NH(C 1-3 alkyl) and N(C 1-3 alkyl) 2 ;
R 1 is H, F, Cl, CN, OH, C 1-3 alkoxy, —OC(O)O(C 1-3 alkyl), —OC(O)NH(C 1-3 alkyl), C 1-3 alkyl, C 1-3 haloalkyl, or C 3-6 cycloalkyl;
R 2 is H, C 1-3 alkyl, C 1-3 haloalkyl or cyclopropyl;
R 3 , R 4 , and R 5 are each independently selected from H, halogen, OH, CN, amino, NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl and C 1-4 haloalkoxy;
alternatively, R 4 and R 5 in combination, together with the carbon atoms to which they are attached, form a 5, 6, or 7-membered fused aryl, a 5, 6, or 7-membered fused cycloalkyl, a 5, 6, or 7-membered fused heteroaryl, or a 5, 6, or 7-membered fused heterocycloalkyl, each optionally substituted by 1, 2 or 3 substituents independently selected from halogen, OH, CN, amino, NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl and C 1-4 haloalkoxy;
R 6 and R 7 are each independently selected from H, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and C 1-4 haloalkyl; wherein said C 1-4 alkyl forming R 6 or R 7 is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, OH, CN, C 1-3 haloalkyl, C 1-4 alkoxy, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , NR c1 S(O) 2 R b1 and S(O) 2 NR c1 R d1 ;
alternatively, R 6 and R 7 , together with the carbon atom to which they are both attached, form a C 3-6 cycloalkyl group that is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, OH, CN, and C 1-4 alkyl;
R a1 , R b1 , R c1 and R d1 , at each occurrence, are independently selected from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, wherein said C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl groups forming R a1 , R b1 , R c1 and R d1 are each optionally substituted with 1, 2, or 3 substituents independently selected from C 1-4 alkyl, halo, CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 NR c2 C(O)OR a2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 and S(O) 2 NR c2 R d2 ;
or R c1 and R d1 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group that is optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, halo, CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 , NR c2 C(O)OR a2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 and S(O) 2 NR c2 R d2 ; and
R a2 , R b2 , R c2 and R d2 are each independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl forming R a2 , R b2 , R c2 and R d2 are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, OH, CN, amino, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl and C 1-6 haloalkoxy.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring A is C 6-10 aryl optionally substituted with 1 or 2 substituents each independently selected from R A .

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein ring A is phenyl optionally substituted with 1 or 2 substituents each independently selected from R A .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring A is 5-10 membered heteroaryl optionally substituted with 1 or 2 substituents each independently selected from R A .

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein ring A is a pyridinyl, pyrimidinyl, thiazolyl, quinolinyl, or furopyridinyl, each optionally substitute

Assignees

• Incyte Corp

Inventors

• Vechorkin Oleg
• Feng Hao
• Li Yun-Long
• Mei Song
• Wang Anlai
• Zhu Wenyu
• Zhuo Jincong

Classifications

• C07D405/14

  containing three or more hetero rings · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title

• C07D409/14

  containing three or more hetero rings · CPC title